Synthesis of Functionalized 2,3-Dihydro-5 H -[1,3]thiazolo[2,3- b ]quinazolin-5-one via Intramolecular Electrophilic Cyc
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hesis of Functionalized 2,3-Dihydro-5H-[1,3]thiazolo[2,3-b]quinazolin-5-one via Intramolecular Electrophilic Cyclization N. M. Kuta,*, M. Yu. Onyskoa, and V. G. Lendela a
Uzhgorod National University, Uzhgorod, 88000 Ukraine *e-mail: [email protected]
Received March 31, 2020; revised April 21, 2020; accepted April 21, 2020
Abstract—3-(2-Methylprop-2-en-1-yl)-2-sulfanylidene-7-(trifluoromethyl)-2,3-dihydroquinazolin-4(1H)-one reacted with halogens (bromine and iodine), chalcogen tetrahalides, and p-methoxyphenyltellurium trichloride in a regioselective manner to give linearly fused 2-halomethyl-2-methyl-5-oxo-8-(trifluoromethyl)-2,3-dihydro5H-[1,3]thiazolo[2,3-b]quinazolinium trihalides, 2-methyl-5-oxo-2-[(trihalo-λ4-chalcogenyl)methyl]-8-(trifluoromethyl)-2,3-dihydro-5H-[1,3]thiazolo[2,3-b]quinazolinium halides, and 2-{[dichloro(4-methoxyphenyl)λ4-tellanyl]methyl}-8-(trifluoromethyl)-2,3-dihydro-5H-[1,3]thiazolo[2,3-b]quinazolin-5-one, respectively. Keywords: electrophilic cyclization, halogen-containing electrophile, p-methoxyphenyltellurium trichloride, regioselectivity, 3-(2-methylprop-2-en-1-yl)-2-sulfanylidene-7-(trifluoromethyl)-2,3-dihydroquinazolin-4(1H)one, 2,3-dihydro-5H-[1,3]thiazolo[2,3-b]quinazolin-5-one
DOI: 10.1134/S1070428020070088 Functionalized quinazolines and their fused derivatives are promising as biologically active compounds or their precursors. Oxo (thioxo) quinazolines exhibit anticancer, antiviral, antifungal, and antibacterial properties [1–8]. Among the series of quinazoline derivatives, a particular place is occupied by fluorinated compounds as fluorine-containing heterocycles are structural fragments of many drugs [9–14]. An efficient method of synthesis of fused quinazoline systems is based on intramolecular electrophilic heterocyclization of alkenyl-substituted heterocycles. Electrophilic heterocyclization underlies a convenient and controllable method of fusion of a thiazole or thiazine ring to pyrimidine scaffold [15–18] and its fused derivatives such as quinazoline [19–22], thieno[2,3-d]pyrimidine, [22–26], pyrazolo[3,4-d]pyrimidine [27–31], pyrido[2,3-d]pyrimidine [32], pyrido[3,4-d]pyrimidine [33],
and pyrido[3,2-d]pyrimidine [34]. Therefore, study of electrophilic cyclization of 3-alkenyl-2-sulfanylidenequinazolin-4-one derivatives by the action of halogencontaining electrophiles and the effect of a trifluoromethyl substituent on the regioselectivity of the reaction is an important problem. In this work, the subject for study was 3-(2-methylprop-2-en-1-yl)-2-sulfanylidene-7-(trifluoromethyl)2,3-dihydroquinazolin-4(1H)-one (1) which was synthesized in a high yield (92%) from 2-amino-4-(trifluoromethyl)benzoic acid and 2-methylprop-2-en-1-yl isothiocyanate in the presence of triethylamine (Scheme 1). Molecule 1 possesses several nucleophilic centers capable of being attacked by electrophiles, in particular the exocyclic C=C double bond of the 3-alkenyl substituent and exocyclic oxygen and sulfur atoms, so that two directions of intramolecular electro-
Scheme 1. O COOH
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